We plan to separate human peripheral blood monocytes, T cells and B cells and study the cyclic AMP response to PGEl in each cell type. This will first be done for normal individuals then in patients with RA (peripheral blood and synovial fluid) and SLE. We plan to study the regulation of prostaglandin synthesis in peripheral blood neutrophils during phagocytosis. We intend first to evaluate the effects of corticosteroids (for example 10 to the minus 4th power M-10 to the minus 10th power M hydrocortisone) and then of colchicine. We plan to study cyclic nucleotide metabolism in cells of mice (and hopefully of man) with the Chediak-Higashi syndrome. We intend to assay cyclic GMP generation in response to concanavalin A. We have begun to culture synovial lining cells, a population of which is phagocytic and which in fact become the center of the inflammatory lesion in the rheumatoid joint. We plan to investigate the possibility that cells in the rheumatoid synovium do not clear immune complexes as well as normal cells, resulting in release of joint damaging proteases and collagenases. BIBLIOGRAPHIC REFERENCES: Oliver, J.M., R.B. Zurier, R.D. Berlin. Concanavalin A cap formation on polymorphonuclear leucocytes of normal and beige (Chediak-Higashi) mice. Nature 253:471, 1975. Zurier, R.B. Rheumatoid Disease. An overview. Connecticut Medicine. 39:348, 1975.